The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program (NTP). The findings may or may not have been peer reviewed and were not evaluated in accordance with the Explanation of Levels of Evidence for Reproductive Toxicity criteria (see http://ntp.niehs.nih.gov/ntp/htdocs/levels/09_3566_NTP_ReproTOX_R1.pdf or with the Explanation of Levels of Evidence for Developmental Toxicity criteria (see http://ntp.niehs.nih.gov/ntp/Test_info/NTP_DevTox20090507.pdf) established by the NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of the NTP or the US Government.
4-Chloronitrobenzene (4CNB), a chemical intermediate in the manufacture of pharmaceuticals, dyes and other chemical products, was tested for its effects on fertility and reproduction in Swiss CD-l mice according to the Continuous Breeding protocol. It was administered via gavage. In the dose-range-finding study, all animals in the 640 mg/kg dose group died and animals in the 320 mg/kg group became cyanotic. Dose levels for Task 2 were set at 62.5, 125 and 250 mg/kg b.wt./day. Male and female mice were continuously exposed for a 7-day pre cohabitation and a 98-day cohabitation period (Task 2). Weights of pups delivered during the 98-day continuous breeding phase to dams in the 125 and 250 mg/kg groups were lower than controls. In the final litter of the continuous breeding phase, the proportion of pups born alive and the pup survival and weight gain during lactation were adversely affected at 250 mg/kg. Most of the 250 mg/kg b.wt. group animals were cyanotic at the time of F1 mating. In the F1 mating, the proportion of F2 pups born alive and live F2 pup weights were significantly reduced in the 250 mg/kg 4CNB group. The average estrous cycle length in the F1 females was significantly increased. At terminal sacrifice, liver weight, and liver-to-body weight ratios were increased in both F1 sexes, and spleens were enlarged while body weights were unchanged. Thus, in the presence of cyanosis and increased liver weights, 4CNB decreased pup birth weights as well as postnatal survival and weight gain.
Report Date: July 1991